APPENDIX 2

Francisella tularensis At-Risk Populations:

• Taxidermists, landscape workers, hunters Disease Agent: • A threat as a bioterrorist weapon for susceptible • Francisella tularensis populations

Disease Agent Characteristics: Vector and Reservoir Involved:

• Gram-negative coccobacillus, aerobic, nonmotile, • Ixodid ticks (Dermacentor variabilis, D. andersoni, nonspore-forming bacterium Amblyomma americanum) • Order: Thiotrichales; Family: Francisellaceae • Biting flies, specifically the deer fly (Chrysops discalis) • Size: 0.2-0.7 mm ¥ 0.2 mm • Mosquitoes in Sweden, Finland, and the former • Nucleic acid: The genome of Franciscella tularensis is Soviet Union 1892 kb of DNA. • Infected mammals are the reservoir. • While the organism grows in appropriate cell-free bacteriologic media, it is widely regarded to be an Blood Phase: intracellular pathogen. • Bacteremia can persist for weeks in symptomatic • The organism survives long-term freezing (i.e., up to 3 infections; asymptomatic bacteremia has not been years in frozen rabbit meat). demonstrated. • 10% bleach can be used for surface decontamination. • Agent found in monocytes

Disease Name: Survival/Persistence in Blood Products: • Tularemia • Unknown • Rabbit fever Transmission by Blood Transfusion: Priority Level: • Theoretical • Scientific/Epidemiologic evidence regarding blood safety: Theoretical Cases/Frequency in Population: • Public perception and/or regulatory concern regard- ing blood safety: Absent • Approximately 100-125 cases reported in the US each • Public concern regarding disease agent: Very low, but year low in regions where outbreaks have occurred • In recent years, a seasonal increase in incidence has occurred (late spring and summer), when arthropod Background: bites are most common. • Outbreaks of tularemia in the US have been associ- • Occurs naturally in several areas of the US, usually in ated with muskrat handling, tick bites, deerfly bites, rural areas. Historically, most cases of tularemia and lawn mowing or cutting brush. occurred in the summer (arthropod bites) and winter • Sporadic cases in the US have been associated with (hunters coming into contact with infected rabbit contaminated drinking water and various laboratory carcasses). exposures. • First described in the US in 1911 and has been reported from all states except Hawaii Incubation Period: • Removed from the list of nationally notifiable dis- eases in 1994, but it was reinstated in 2000 because of • Usually 3-5 days, but can take weeks increased concern about potential use of F.tularensis Likelihood of Clinical Disease: as a biologic weapon • Classified among the highest priority for bioterrorism • Disease likelihood will vary based on exposure rate agents by the CDC (Category A) and immune status of host. Immunocompromised persons are more likely to have complications. Common Human Exposure Routes: Primary Disease Symptoms: • Inhalation: Bacterium aerosolized when animals skinned or shredded by lawnmowers • Skin ulcers, swollen and painful lymph nodes, sudden • Tick or fly bites by infected vectors fever, chills, headaches, diarrhea, muscle aches, joint pain, dry cough, and progressive weakness Likelihood of Secondary Transmission: • Pneumonia-like symptoms also are possible, particu- • Highly unlikely larly when the agent is inhaled.

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Severity of Clinical Disease: Leukoreduction Efficacy:

• More severe infections can be and are fatal, particu- • Unknown larly if left untreated.

Mortality: Pathogen Reduction Efficacy for Plasma Derivatives:

• Varies by exposure route and subspecies but • Specific data indicate that the multiple steps in the untreated inhalation tularemia may have a mortality fractionation process are robust and capable of inac- rate of from 30 to 60%. tivating and/or removing bacteria at concentrations Chronic Carriage: that may be present in plasma.

• Unknown in humans Other Prevention Measures: Treatment Available/Efficacious • A vaccine is presently under review but is not • Once diagnosed, infection is treatable with anti- approved for use in the US. biotics (tetracyclines and fluoroquinolones). Antibi- • Vector avoidance otic treatment is efficacious. Agent-Specific Screening Question(s): Other Comments: • No specific question is in use. • Outbreaks of pneumonic tularemia, particularly in • Not indicated because of the low incidence of infec- low-incidence areas, should prompt consideration of tion and lack of evidence of transfusion transmission. bioterrorism. • No sensitive or specific question is feasible. • Under circumstances of a bioterrorism threat, the Suggested Reading: need for and potential effectiveness of specific donor- screening questions would need to be addressed. 1. Centers for Disease Control and Prevention. Tularemia—United States, 1990-2000. Morb Mortal Laboratory Test(s) Available: Wkly Rep MMWR 2002;51:182-4. • No FDA-licensed blood donor screening test exists. 2. Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, • Culture, microagglutination based on fourfold rise in Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer titers, EIA, and PCR available J, Layton M, Lillibridge SR, McDade JE, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Tonat K; Currently Recommended Donor Deferral Period: Working Group on Civilian Biodefense. Tularemia as a • No FDA Guidance or AABB Standard exists. biological weapon: medical and public health man- • Prudent practice would be to defer donor until signs agement. JAMA 2001;285:2763-73. and symptoms are gone and any course of treatment 3. Farlow J, Wagner DM, Dukerish M, Stanley M, Chu M, is complete. Kubota K, Petersen J, Keim P. Francisella tularensis in the United States. Emgerg Infect Dis 2005;11:1835- Impact on Blood Availability: 41. • Agent-specific screening question(s): Not applicable; 4. Feldman KA, Enscore R, Lathrop S, Matyas BT, in response to a bioterrorism threat, impact of a local McGuill M, Schriefer ME, Stiles-Enos D, Dennis DT, deferral would be significant. Petersen LR, Hayes EB. An outbreak of primary pneu- • Laboratory test(s) available: Not applicable monic tularemia on Martha’s Vineyard. N Engl J Med 2001;345:1601-6. Impact on Blood Safety: 5. Schmid GP, Kornball AN, Connors CA, Patton C, • Agent-specific screening question(s): Not applicable; Carney J, Hobbs J, Kaufmann AF. Clinically mild tula- unknown impact in response to a bioterrorism threat remia associated with tick-borne Francisella tularen- • Laboratory test(s) available: Not applicable sis. J Infect Dis 1983;148:63-7.

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